Search Results (14,564)

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, characterized by hyperandrogenism, insulin resistance, and ovarian dysfunction. Current therapies are often associated with adverse effects, highlighting the need for safer therapeutic alternatives. Peganum harmala (P. harmala), a medicinal plant rich in bioactive metabolites, was investigated through in silico approaches to identify compounds with predicted binding affinity for the androgen receptor (AR), steroid 17α-hydroxylase/17,20-lyase (CYP17A1), and glycogen synthase kinase-3 beta (GSK-3β). GC-MS analysis of P. harmala leaf essential oil collected in Riyadh, Saudi Arabia, identified 109 compounds, with terpenoids as the dominant class (21.89%). The major constituents were cis-chrysanthenyl acetate (3.48%), cis-β-damascenone (3.06%), farnesylacetone (1.44%), β-calacorene (1.36%), dihydroedulan II (1.04%), and trans-calamenene (0.46%). In silico ADMET evaluation indicated that most compounds complied with Lipinski’s rule of five and showed favorable predicted pharmacokinetic properties. Safety profiling suggested an overall acceptable toxicity profile, with minimal predicted CYP450 inhibition, except for L11, which showed broader inhibitory potential. Molecular docking showed that L15 (trans-calamenene), L14 (dihydroedulan II), L6 (β-calacorene), L3 (farnesylacetone), and L8 exhibited higher predicted binding affinity toward the androgen receptor; L3, L10 (cis-β-damascenone), and L16 (cis-chrysanthenyl acetate) interacted with CYP17A1, while L3, L9, and L6 exhibited higher affinity toward GSK-3β. Overall, these findings provide hypothesis-generating in silico predictions of ligand–target binding affinities and drug-likeness profiles. These computational findings highlight the importance of future experimental investigations to substantiate the biological activity, pharmacokinetic behavior, and safety profile of P. harmala constituents. Full article

The global rise in obesity and metabolic disorders has intensified interest in dietary bioactives capable of improving glycemic control and metabolic health. Inositols, particularly D-pinitol, have emerged as insulin-sensitizing cyclitols with potential metabolic relevance. Carob (Ceratonia siliqua L.), one of the richest natural sources of D-pinitol, represents a promising nutritional matrix for metabolic regulation. This narrative review critically evaluates current evidence on the role of D-pinitol in glucose homeostasis and energy balance, integrating data from chemical characterization studies, mechanistic research, preclinical models, and human clinical trials assessing purified D-pinitol and D-pinitol–rich preparations, particularly from carob-derived sources. Available evidence suggests that D-pinitol may enhance insulin signaling efficiency, primarily through PI3K/Akt-dependent pathways, modulate hepatic metabolic flexibility, and influence endocrine balance without acting as a classical hypoglycemic agent. Preclinical models consistently report improvements in insulin sensitivity, lipid handling, oxidative stress parameters, and tissue-specific metabolic adaptations. In contrast, clinical trials in healthy, prediabetic, and type 2 diabetic individuals show more heterogeneous outcomes, including attenuation of postprandial glycemia, reductions in circulating insulin and HOMA-IR, and modest improvements in lipid and inflammatory markers. Overall, carob-derived D-pinitol appears to act as a potential insulin-sensitizing metabolic modulator with context-dependent effects influenced by metabolic phenotype and food matrix composition. However, available data remains limited and heterogeneous, with most data derived from preclinical studies and relatively small clinical trials. These findings should therefore be interpreted with caution. Larger, longer-term randomized controlled trials using standardized preparations are required to establish clinical relevance and translational applicability. Notably, the contribution of other bioactive components within the carob matrix cannot be excluded. Full article

Objectives: The objectives of this review are to explore the effects of various nutrition and exercise lifestyle interventions on pregnancy outcomes in individuals with, or at risk of, gestational diabetes mellitus (GDM), as well as to examine whether interventions that are culturally and/or religiously sensitive influence clinical and behavioural outcomes. Methods: This study was conducted as a narrative review. PRISMA was used solely as a reporting guide to enhance transparency in the search and study selection process. PubMed/MEDLINE, CINAHL, and Scopus were searched for studies published up to November 2025. Intervention-based studies evaluating nutrition, physical activity, or combined lifestyle interventions targeting either GDM incidence, insulin use, or glycemic outcomes were included. Forty-three studies met eligibility criteria. Study designs consisted primarily of randomized controlled trials (RCTs) with one case–control and one quasi-experimental design trial. Results: Combined lifestyle interventions generally showed the most consistent improvements in glycemic control; however, findings were not uniform across all studies, and reporting on insulin outcomes was limited. The Mediterranean, low-glycemic index (LGI) and DASH diets, along with supervised, prenatal exercise programs with low–moderate intensity, delivered at least three times per week, were effective in managing GDM. Regarding culturally or religiously sensitive interventions, only one study was identified. Conclusions: Lifestyle interventions may improve glycemic outcomes in GDM; however, further high-quality research is needed, particularly studies incorporating culturally and religiously sensitive approaches and improved reporting of insulin-related outcomes. Full article

Background: Sex-related differences in insulin sensitivity during adolescence remain incompletely understood, particularly in the context of obesity. Whether these differences reflect variations in basal insulin resistance or dynamic insulin responses remains unclear. Objective: To investigate sex differences in glucose and insulin responses during the oral glucose tolerance test (OGTT) and to explore mechanisms underlying potential dissociation between glycemic and insulinemic profiles. Methods: A cross-sectional analysis of 753 adolescents with obesity who underwent a standard oral glucose tolerance test (OGTT). Plasma glucose and insulin were measured at fasting and at 30, 60, 90, and 120 min. Mixed-effects models were used to examine glucose and insulin trajectories over time, including sex-by-time interactions, and to adjust for body mass index standard deviation score (BMI_SDS), pubertal stage (Tanner), metabolic syndrome (MetS), and body composition (resistance index). Multiple linear regression models were fitted to assess associations of sex with HOMA-IR, HOMA-β, total area under the curve (AUC), and phase-specific insulin AUCs. Results: Glucose trajectories during OGTT were similar between sexes, with no significant sex or sex-by-time interaction effects after adjustment. In contrast, insulin trajectories differed significantly by sex (sex-by-time interaction β = −0.10, p < 0.001). Boys exhibited higher baseline insulin levels and greater total insulin exposure (β = −11.2, p < 0.001), independent of BMI_SDS, pubertal stage, MetS, and body composition. Sex differences were sustained across all OGTT phases. HOMA-IR did not differ by sex, whereas HOMA-β showed a sex-related difference. BMI was positively associated with both basal and dynamic insulin measures. Conclusions: In adolescents with obesity, sex differences are characterized by altered dynamic insulin responses rather than differences in glycemic control. Boys exhibit greater compensatory insulin exposure during glucose challenge, independent of BMI-based adiposity, BIA-derived body composition and pubertal development. Full article

Background/Objectives: The main cause of death in patients with chronic kidney disease (CKD) is of cardiovascular origin. Entropy-based analysis of physiological signals reflects system irregularity, complexity, and adaptive capacity. Amplitude-aware permutation entropy (AAPE) is a signal analysis method suitable for assessing complex cardiovascular dynamics, and growing evidence suggests that measures of physiological signal variability and complexity may have prognostic value. This study aimed to evaluate whether AAPE can predict mortality in CKD patients undergoing hemodialysis (HD), with and without diabetes. The aim of this study was to assess whether AAPE analysis of cardiovascular signals following the administration of a glucose bolus directly into the extracorporeal circuit during hemodialysis (HD)—a method originally used to treat intradialytic hypotension and to study the kinetics of glucose, insulin, and C-peptide in patients with and without type 2 diabetes—can predict mortality in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD), both with and without diabetes. Methods: After seven years of follow-up, mortality outcomes were analyzed in relation to AAPE-derived parameters. Results: Higher mortality was associated with smaller differences in AAPE of mean arterial pressure (MAP) and diastolic arterial pressure (DIA) before and after intravenous glucose administration (p = 0.009 and p = 0.016, respectively). Higher tonicity was associated with higher survival (p = 0.01). Additionally, greater reductions in AAPE of systolic arterial pressure (SYS) and larger differences in AAPE of ejection time (EJT) and total peripheral resistance (TPR) were associated with increased mortality. Conclusions: These findings suggest that entropy analysis reflects cardiovascular adaptability and may serve as a prognostic biomarker in HD patients. Full article

Background: Effective sick-day management, including ketosis home management aimed at preventing diabetic ketoacidosis (DKA), is essential for families living with a child/adolescent with type 1 diabetes (T1D). Methods: Adolescents living with T1D and caregivers of younger children living with T1D were invited to participate in an interview consisting of five parts: (I) demographic data, (II) subjective self-ratings on competence in ketosis home management, (III) objective assessment of competence in ketosis home management using a standardized clinical case scenario consisting of 10 management steps, in which participants were asked to describe the actions they would take to prevent DKA, and (IV) practical demonstrations to objectively assess skills in (IVa) urine dipstick self-testing and (IVb) insulin administration, (V) household availability of (Va) urine dipsticks and (Vb) insulin cartridges. Results: (I) We enrolled 61 adolescents and 79 caregivers. (II) Competence in ketosis home management was subjectively self-rated as good to very good. (III) Adolescents reported 4 (median; Q25/Q75 3/5) and caregivers 5 (4/5) of 10 management steps. Never self-testing ketone levels was reported by 33% of adolescents and 11% of caregivers. (IVa) At least one handling error occurred in 100% of adolescents’ and in 98% of caregivers’ practical demonstrations of urine dipstick self-testing and in (IVb) 98% of adolescents’ and 98% of caregivers’ insulin administrations. (Va) Altogether urine dipsticks were available in 43% of households, whereas (Vb) insulin cartridges were available in 78% of households. Conclusions: Our results demonstrate a mismatch between challenges in ketosis home management and high subjective self-ratings. Full article

The global rise in obesity and cardiometabolic disease represents a major public health concern and contributes significantly to cardiovascular morbidity and mortality. Contemporary Western dietary patterns and excess adiposity are strongly associated with atherosclerotic cardiovascular disease. Although pharmacologic therapies have expanded, lifestyle interventions remain the cornerstone of prevention and management. However, identifying sustainable and effective dietary approaches continues to be challenging given the wide range of available nutrition regimens. Intermittent fasting (IF) has emerged as a promising strategy for weight reduction and metabolic improvement. In this article, we review the physiological effects of IF, including metabolic switching, ketosis, and improvements in insulin sensitivity and inflammatory regulation. We also evaluate clinical evidence regarding the impact on cardiovascular risk, as well as its safety and tolerability. We examine the hormonal responses to IF based on sex. While early studies raised concerns regarding potential reproductive and endocrine disturbances, recent data suggest beneficial effects in both males and females. IF may modestly reduce testosterone in men without impairing muscle mass or strength and may improve metabolic and reproductive outcomes in women, particularly those with hyperandrogenic conditions such as polycystic ovarian syndrome, with favorable effects also observed in postmenopausal women, especially when combined with physical activity. Full article

Background: We aimed to study the association between accelerometer-measured physical activity and metabolic markers of diabetes in a nationwide representative sample of U.S. adults. Methods: This cross-sectional analysis included 1259 adults aged ≥18 years from the 2003–2004 National Health and Nutrition Examination Survey (NHANES), the only cycle incorporating objective accelerometry. Physical activity was assessed using hip-worn accelerometers, with moderate-to-vigorous physical activity (MVPA) and sedentary time derived from validated count thresholds. Metabolic outcomes included fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and insulin resistance estimated by the Homeostatic Model Assessment (HOMA-IR). Survey-weighted linear regression models accounting for the complex sampling design were applied, with sequential adjustment for demographic, socioeconomic, anthropometric, and behavioral covariates. Sensitivity analyses tested alternative MVPA thresholds and wear-time criteria. Results: In unadjusted models, higher MVPA was inversely linked with fasting glucose and insulin concentrations; but, these associations were attenuated after full multivariable adjustment. In contrast, MVPA established a constant inverse association with insulin resistance. Higher MVPA was connected with lower HOMA-IR values, and this relationship remained statistically significant in fully adjusted models and across all sensitivity analyses (all p < 0.001). Associations between sedentary time and metabolic markers were non-sustainable after multivariable adjustment. No significant effect modification by sex was detected. Conclusions: Objectively measured moderate-to-vigorous physical activity is independently linked with lower insulin resistance in U.S. adults. These results emphasize the value of accelerometer-based assessments for identifying early metabolic risk and reinforce physical activity promotion as a key strategy for improving insulin sensitivity. Full article

Background: Artificial intelligence (AI) is increasingly incorporated into nutrition research and practice; however, the extent of its clinical integration and impact on health outcomes remains unclear. This systematic review evaluated how AI-based systems have been implemented in human nutritional interventions and summarized reported outcomes. Methods: PubMed, Scopus, Google Scholar, SpringerLink, JMIR, and MDPI were searched from January 2020 to March 2025 (search completed in March 2025). Randomized controlled trials and prospective or retrospective cohort studies published in English or Spanish were included if they evaluated AI-driven nutritional interventions in human populations and reported health-related outcomes. Risk of bias was assessed using RoB 2 and ROBINS-I. A qualitative synthesis was performed. Results: Sixteen studies involving 10,863 participants were included. Most were randomized controlled trials targeting metabolic disorders, particularly type 2 diabetes and obesity. Eleven studies evaluated metabolic outcomes, including HbA1c, body weight, fat mass, lipid levels, and insulin resistance indices. Six studies assessed gastrointestinal symptom severity scores, and two examined quality-of-life or patient-reported outcomes. Several trials reported short-term improvements favoring AI-supported interventions in glycemic control, weight reduction, and symptom severity. However, effects were heterogeneous and often observed within multimodal programs, limiting attribution of outcomes solely to the AI component. Conclusions: AI integration in nutrition remains in an early phase of clinical implementation. Although preliminary findings suggest potential benefits, interpretation should be cautious given methodological heterogeneity and moderate-to-high risk of bias across studies. Larger, rigorously designed investigations are required to determine sustained clinical effectiveness. Full article

Background: Metabolic syndrome (MetS) is a cluster of pathologies (obesity, dyslipidemia, insulin resistance, hypertension) that affects over one quarter of old adults. MetS is a condition that markedly increases the susceptibility of various organs to dysfunctionality and is associated with the development of oxidative stress. The existing guidelines point out that exercise is highly advantageous for patients with MetS. However, there is a need for specific guidance and clinical evidence. Objective: This study aimed to investigate the effects of a moderate aerobic exercise program on older women without and with MetS. Methods: A total of 120 women aged 60–70 years old were recruited and divided into two groups: healthy old women (HOW, N = 60) and old women with MetS (OW-MetS, N = 60). Anthropometric values, biochemical parameters and markers of oxidative damage were evaluated before and after moderate aerobic exercise. Exercise was performed five days per week for three months (64 sessions). Each exercise session consisted of 40 min and included the following: (a) five minutes of warm-up exercise; (b) ten minutes of flexibility exercise with resistance using own weight and coordination; (c) twenty minutes of moderate-intensity aerobic exercise (heart rate max between 60% and 70%); and (d) five minutes to cool down/stretching with respiratory techniques. Results: A significant decrease in anthropometric variables was generated by the exercise program [waist circumference 4.35 cm (p < 0.05) in OW-MetS, body fat −1.55, −1.39% (p < 0.05) and muscle mass 0.8, 1.1% (p < 0.05) in HOW and OW-MetS, respectively]. The exercise program resulted in beneficial changes in all biochemical parameters in both groups. Importantly, HOMA values showed a significant decline of −0.85 and −6.17 in HOW and OW-MetS, respectively. Furthermore, oxidative stress was present in the OW-MetS group, which was reduced by the exercise program, resulting in a decrease in protein damage [formazan 45% and 42% in HOW and OW-MetS respectively] and an increase in antioxidant defenses (thiol groups 36%, 99% and GPx 55%, 20% in HOW and OW-MetS, respectively). Conclusions: The data of this study show that moderate aerobic exercise may be potentially useful in treating and preventing MetS in older patients. Full article

Background/Objectives: Sphingosine-1-phosphate (S1P) is implicated in glycemic control. However, its circulating levels and clinical significance in type 2 diabetes mellitus (T2DM) remain controversial. We assessed plasma S1P levels in T2DM patients, its associations with metabolic parameters and complications, and explored its biomarker potential and non-linear (U-/J-shaped) relationships. Methods: This cross-sectional study enrolled 140 patients with T2DM and 63 matching healthy controls. Plasma S1P was measured by competitive ELISA. Statistical analyses included comparisons, correlation, ROC analysis, multivariable logistic regression, and quadratic/spline regression for U-shaped relationships. Results: Plasma S1P was significantly elevated in T2DM patients [1256.7 (149.4–1510.0) ng/mL] compared to controls [1075.1 (202.0–1510.0) ng/mL; p < 0.001]. S1P correlated positively with age, disease duration, HbA1c, insulin resistance, TyG index, triglycerides, systolic blood pressure, and negatively with HDL-C. Patients with complications had higher S1P than those without (p = 0.001), with progressive increases from retinopathy to nephropathy to mixed complications. Insulin-treated patients exhibited the highest S1P levels (p < 0.001). ROC analysis showed moderate diagnostic accuracy (AUC = 0.724). S1P is an independent associated factor with complications (OR = 1.18 per 100 ng/mL, p = 0.003). Non-linear analysis revealed a U-shaped relationship with HDL-C (optimal S1P: 1100–1350 ng/mL) and a J-shaped relationship with complication risk (threshold ~1250 ng/mL). Conclusions: Plasma S1P is elevated in T2DM and correlates with disease severity, glycemic control, insulin resistance, and complications. S1P demonstrates moderate biomarker potential and exhibits non-linear U-/J-shaped relationships with metabolic parameters, suggesting an optimal therapeutic window of 1100–1280 ng/mL. These findings support S1P as a marker of cumulative disease burden and a potential therapeutic target. Full article

Zinc-α2-glycoprotein (ZAG) is a novel adipokine with a plethora of functions meaningful for the regulation of adipose tissue and insulin sensitivity. Despite research, the role of ZAG in the course of childhood obesity is not fully understood. The aim of this study is to investigate whether the levels of ZAG can be used as a predictive or monitoring biomarker of adolescent obesity. Secondly, to determine the cut-off value of ZAG in blood serum in adolescents with obesity. The study included a group of 77 adolescent patients, including 59 obese patients, and 18 without obesity as healthy control subjects. All study participants had their biochemical parameters assessed by a certified medical laboratory. The recommendations of the Polish Society of Hypertensions were used to assess the blood pressure measurements in each group. ELISA enzyme immunoassays (R&D Systems, Minneapolis, MN, USA) were used to detect serum levels of ZAG. Our study showed that obese children and adolescents have significantly higher body mass, cholesterol, LDL-cholesterol, triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), but lower serum ZAG levels compared to the healthy control subjects. Furthermore, in our study, we found that median ZAG values were comparable between females and males within the same obesity category (median female ZAG level: 2.84, median male ZAG level: 2.89) and healthy control participants (median female ZAG level: 5.20, median male ZAG level: 4.99). Serum ZAG concentrations were significantly lower in obese participants (2.86 ± 0.40 mg/L) than in the control group (5.10 ± 0.74 mg/L; p < 0.001). The multivariable Firth’s logistic regression model, incorporating the selected factors, revealed a significant association between obesity and ZAG. ROC curve analysis indicated strong discriminatory ability of ZAG for identifying obesity, with a proposed cut-off value of 3.62 mg/L. Circulating ZAG level is significantly reduced in children and adolescents with obesity. An important finding of our study is the detection of a cutoff value for serum ZAG levels. Furthermore, the use of the Least Absolute Shrinkage and Selection Operator (LASSO) model can be considered a valuable contribution to defining ZAG as an independent factor associated with obesity. Full article

Background/Objectives: Clear cell renal cell carcinoma is the most common subtype of kidney cancer and exhibits marked biological heterogeneity, even among tumors of the same histological grade. Although tumor grade remains a key prognostic parameter, the molecular alterations associated with tumor differentiation are not fully understood. This study aimed to evaluate grade-dependent tissue-level expression patterns of proteins involved in cellular stress response, growth regulation, stemness, and apoptosis in clear cell renal cell carcinoma. Methods: Protein expression of heat shock protein 70, insulin-like growth factor 1, octamer-binding transcription factor 4, and apoptosis-inducing factor were analyzed in human clear cell renal cell carcinoma samples and normal renal cortex. Low-grade and high-grade tumors were compared using immunofluorescence staining combined with semi-quantitative and quantitative image analysis. The proportion of positive signals and the number of positive cells were assessed across tissue compartments. In addition, publicly available transcriptomic data from The Cancer Genome Atlas kidney renal clear cell carcinoma cohort were analyzed to explore associations between gene expression levels and overall survival. Results: Distinct grade-dependent expression patterns were observed for all investigated proteins. Heat shock protein 70, insulin-like growth factor 1, and octamer-binding transcription factor 4 showed a higher expression in normal renal tissue with a progressive reduction across tumor grades. In contrast, apoptosis-inducing factor exhibited increased expression in tumor tissue, particularly in low-grade tumors, with a relative decrease in high-grade carcinomas. Stromal compartments of tumor tissue showed minimal or no expression for most markers. Transcriptomic survival analysis did not reveal significant differences in overall survival between high- and low-expression groups for any of the investigated genes. Grade-stratified transcriptomic analysis of the TCGA KIRC cohort revealed consistent patterns for HSP70 family members and OCT4, with progressive grade-dependent mRNA reduction toward higher grades, while IGF1 showed an inverse mRNA trend and AIFM1 showed a uniform reduction across all tumor grades without a clear inter-grade pattern. Conclusions: The findings demonstrate that stress response, growth-related, stemness-associated, and apoptotic proteins display distinct grade-dependent tissue-level expression patterns in clear cell renal cell carcinoma, with the expression profiles of high-grade tumors being of particular translational interest given the aggressive clinical behavior and therapeutic resistance characteristic of this disease stage. These alterations appear to reflect tumor differentiation and biological behavior rather than independent prognostic value, highlighting the complexity of molecular regulation in renal tumorigenesis. Full article

2,3′,4,4′,5-Pentachlorobiphenyl (PCB118) is a persistent environmental pollutant associated with adverse female reproductive outcomes; however, its effects on uterine function and epigenetic regulation remain incompletely understood. This study investigated whether PCB118 disrupts uterine decidualization and angiogenesis through miRNA-mediated regulatory pathways. Human endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs) were exposed to an environmentally relevant, non-cytotoxic concentration of PCB118. Decidualization and angiogenesis were evaluated in vitro, and underlying mechanisms were investigated using molecular and miRNA-based approaches. In vivo validation of miR-542-3p expression was performed in pregnant mice following PCB118 exposure. PCB118 exposure was associated with reduced expression of decidualization markers, including prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP-1), as well as impaired angiogenic capacity in HUVECs. PCB118 treatment was accompanied by increased miR-542-3p expression, which was associated with decreased integrin-linked kinase (ILK) levels and changes in transforming growth factor beta 1 (TGF-β1) and total Smad2 protein abundance. ILK overexpression partially restored decidualization and angiogenesis-related phenotypes, supporting a functional involvement of ILK in these processes. Consistently, elevated miR-542-3p expression was observed in murine endometrial tissues following PCB118 exposure, suggesting physiological relevance in vivo. PCB118 exposure is associated with impaired decidualization and angiogenesis, potentially involving dysregulation of the miR-542-3p/ILK signaling axis, suggesting a potential role for epigenetic modulation in PCB118-associated reproductive dysfunction. Full article

Oxidative stress and gut microbiota dysbiosis establish a self-perpetuating loop that disrupts epithelial barrier integrity and fuels chronic inflammatory and metabolic disorders, including inflammatory bowel disease (IBD), metabolic syndrome (MS), and chronic kidney disease (CKD). This systematic review synthesizes mechanistic, preclinical, and clinical evidence linking reactive oxygen species (ROS), microbiota-derived metabolites, and host redox homeostasis, with a focus on probiotic-based interventions. Comprehensive searches of PubMed, Scopus, Web of Science, and Google Scholar (2000–March 2026) identified in vitro, animal, and human studies, as well as systematic reviews and meta-analyses, assessing oxidative biomarkers, microbiome profiles, and barrier function outcomes. Probiotic strains, predominantly Lactiplantibacillus, Bifidobacterium, and emerging next-generation taxa, attenuate oxidative stress by inducing antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GPx)], activating Nrf2 signaling, and restoring short-chain fatty acid (SCFAs) production, thereby lowering malondialdehyde (MDA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) while enhancing total antioxidant capacity (TAC). At the mucosal interface, probiotics strengthen tight junction proteins, suppress NF-κB-mediated cytokine release, and mitigate dysbiosis, contributing to clinically meaningful improvements in disease activity, insulin sensitivity, and uremic toxin burden along gut–liver, gut–kidney, and other gut–organ axes. Overall, current evidence supports probiotics and synbiotics as promising adjuncts for nutrition-driven redox modulation, while highlighting the need for strain-resolved, multi-omics, multicenter trials with standardized redox and microbiome endpoints to optimize dosing strategies and long-term safety. Full article